Naturally occurring chromosomal imbalances are an exceptionally important clinical problem, in part because they are extremely common. Almost 1% of all live births and a much higher percentage of conceptions are affected. Many of the abnormalities involve “extra” chromosomal material, and many of these are so deleterious that they cause spontaneous abortion. Trisomies, in which the fetus carries three of a given chromosome rather than a pair, are usually lethal. Some are not; trisomy 13 (Patau syndrome), trisomy 18 (Edward syndrome), trisomy 21 (Down syndrome), triple-X syndrome, as well as duplications of the X and Y chromosomes (e.g., XXY and XYY) are seen in live births, although babies born with Patau syndrome or Edward syndrome usually do not live more than a year or two.
Down syndrome is extremely common relative to other severe genetic disorders. In the United States alone, over 350,000 people are living with the severe handicaps typical of Down syndrome, and there are millions of affected people around the world. Although Down syndrome children are often happy and highly loved, their disorder greatly impacts them, their entire families, and society. Mental retardation, with poor verbal functioning, is the most debilitating outcome, but there are also other medical issues, including much greater risks of early onset Alzheimer's disease, leukemia, and cardiac defects. Because Down syndrome individuals often are at or just below the threshold of independent functioning, even small increases in function could have significant positive consequences for them and their families.
Although the incidence of Down syndrome increases with the mother's age, 80% of Down syndrome babies are born to women under 35 who are not currently subject to prenatal screening. Upon birth of the Down syndrome baby, the whole family is faced with the enormous challenges associated with caring for and nurturing such a child. For older mothers who do have pre-natal screening, the parents are faced with the heart-wrenching decision of birthing a mentally retarded child or terminating the pregnancy, with no hope of systemic therapy. We believe that whole chromosome therapy would result in a paradigm shift in the minds of many scientists, families, and clinicians, who currently presume that gene therapy for this multi-gene disorder, with such pleiotropic effects, is just not possible.